• Log in with Facebook Log in with Twitter Log In with Google      Sign In    
  • Create Account
              Advocacy & Research for Unlimited Lifespans

- - - - -

Mitochondrial aging: TOM & OGG

  • Please log in to reply
1 reply to this topic


  • Lurker
  • 1

Posted 04 July 2004 - 11:34 AM

In aged cells a paradoxical phenomenon is observed: the DNA repair gene OGG1 transcription is upregulated and the encoded enzyme is shuttled off for transport into mitochondria to repair increased 8-oxoG lesions yet DNA repair function diminishes!

An explanation for this disturbing phenomenon has been demonstrated by the observation that the the OGG1 targeted to mitochondria is unable to enter and becomes sequestered into the mitochondrial membrane. Thus even though the nucleus is producing more DNA repair enzyme to deal with the increasing lesions in the mitochondrial DNA - the enzyme can't get in and do its job.

It is now evident that mitochondrial import function is impaired insofar as the mtDNA repair enzymes OGG1 and UDG are concerned even though other enzymes such as cytochrome c oxidase do not seem to be affected. The authors of the cited paper (1) suggest that the problem with the DNA repair enzymes gaining entry could be associated with oxidative modification of the TOM20 and TOM70 domains of the mitochondrial transport TOM complex and/or HSP70, the mitochondrial heat shock protein.

I credit this finding on bates who originally posted the study (1) in Aging Theories even though he did not underline the implications. It is of particular significance for 2 reasons:

a) In the understanding of why DNA repair function diminishes in aged mitochondria, allowing the formulation of the appropriate strategy for therapeutic interventions. Perhaps overexpression of endogenous DNA repair is not enough or that it may only be limited in OGG1. We need to look further to determine what precisely is the molecular mechanism that inhibits translocation in some proteins. It could be that a simpler intervention can be applied that ensures translocation function in aged cells and thereby maintains mitochondrial function in the aged cell for a longer period.

As of this post a search of the literature has not resulted in any further studies in aged mitochondrial translocation of OGG1. Considering that there are other DNA repair enzymes outside of OGG1 this could either mean that this phenomenon is either isolated in OGG1 type proteins or that researchers have yet to study the effect of an aged TOM complex.

b) In presenting a further challenge to one of the postulates in SENS (2), being that the transfer of mtDNA to the nucleus is a valid intervention. Without ensuring that the path to the mitochondrion is clear any strategy that suggests nuclear to mitochondrial transport in invalid until the problem of the aged mitochondrial translocation complex is solved.

(1) Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):10670-5. Epub 2003 Sep 05
(2) Sci Aging Knowledge Environ. 2003 Nov 5;2003(44):pe30.

#2 Logic

  • Guest
  • 2,650 posts
  • 570
  • Location:Kimberley, South Africa
  • NO

Posted 12 October 2014 - 01:26 PM

I'm bumping this as perhaps C60oo prevents the "oxidative modification of the TOM20 and TOM70 domains of the mitochondrial transport TOM complex and/or HSP70, the mitochondrial heat shock protein" alowing DNA repair enzymes to gain entry to mitochondria???

This could be an argument FOR daily dosing of C60oo as there may be less need to allow for the apoptosis/mitophagy of defective mitochondria???

1 user(s) are reading this topic

0 members, 1 guests, 0 anonymous users